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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000545-40 | EudraCT Number |
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| Name | Class |
|---|---|
| Charite University, Berlin, Germany | OTHER |
| University of Alberta | OTHER |
| Biogen | INDUSTRY |
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This prospective trial will assess the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and efficacy of the fully human CD38 monoclonal antibody felzartamab in kidney transplant recipients with late active or chronic-active ABMR. The study is designed as a randomized, controlled, double-blind pilot phase 2 trial. Participants will be randomized to receive either felzartamab or placebo for a period of six months, and then followed for another six months. After six and twelve months, study participants will be subjected to follow-up allograft biopsies.
This prospective bi-center study (University of Vienna, Charité Universitätsmedizin Berlin; Sponsor: Medical University of Vienna, Vienna, Austria; Funder: MorphoSys AG, Planegg, Germany) is an investigator-driven pilot trial designed to assess the safety&tolerability (primary endpoint), pharmacokinetics, immunogenicity, pharmacodynamics and efficacy (preliminary assessment) of the fully human CD38 monoclonal antibody felzartamab in kidney transplant recipients diagnosed with late active or chronic-active antibody-mediated rejection (ABMR) after kidney transplantation.
Adult renal allograft recipients with anti-HLA donor-specific antibodies (DSA) and biopsy-proven ABMR (Banff 2019 classification) ≥180 days post-transplantation will be identified and recruited at the kidney transplantation outpatient services of the two center sites.
The primary endpoint will be safety and tolerability. Participants will be randomized to receive either felzartamab (intravenous administration) or placebo (1:1 randomization stratified by study site and according to ABMR categories) for a period of 6 months (administration of felzartamab/placebo at day 0, 7, 14, 21, and thereafter in 4-weekly intervals. After six (week 24) and twelve months (week 52), study participants will be subjected to follow-up allograft biopsies.
Primary goals of the trial are to assess the safety, pharmacokinetics and pharmacodynamics (peripheral blood plasma cell and natural killer cell depletion) of a 6-month course of treatment over a period of 12 months. The trial will in addition provide first data on efficacy (progression/activity of rejection, blood biomarkers) and potential associations of treatment with parameters reflecting clinical progression of allograft dysfunction, including the course of estimated glomerular filtration rate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Felzartamab | Active Comparator | 9 doses of felzartamab as an intravenous infusion over 6 treatment cycles at 28 days each. Dosing occurs every week in cycle 1 and every four weeks in cycles 2-6. |
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| Placebo | Placebo Comparator | 9 doses of placebo as an intravenous infusion over 6 treatment cycles at 28 days each. Dosing occurs every week in cycle 1 and every four weeks in cycles 2-6. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Felzartamab | Drug | Intravenous infusion in regular intervals over 6 months |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-emergent adverse events | (Serious) adverse events will be classified using the Medical Dictionary for Regulatory Activities (MedDRA). Documentation of an AE will include the assessment of its relationship with the study drug (unrelated, related) and the severity of AE will be graded on a three-point scale (mild, moderate, severe). | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Felzartamab serum concentration | Total felzartamab serum concentration (ELISA, ng/mL) | At day 0, week 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 44, 48 and 52 |
| Anti-Felzartamab antibodies |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Georg A Böhmig, MD | Department of Internal Medicine III, Medical University of Vienna | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of Vienna | Vienna | 1090 | Austria | |||
| Charité University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32235256 | Background | Doberer K, Klager J, Gualdoni GA, Mayer KA, Eskandary F, Farkash EA, Agis H, Reiter T, Reindl-Schwaighofer R, Wahrmann M, Cohen G, Haslacher H, Bond G, Simonitsch-Klupp I, Halloran PF, Bohmig GA. CD38 Antibody Daratumumab for the Treatment of Chronic Active Antibody-mediated Kidney Allograft Rejection. Transplantation. 2021 Feb 1;105(2):451-457. doi: 10.1097/TP.0000000000003247. | |
| 32171061 |
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| ID | Term |
|---|---|
| C000709267 | felzartamab |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Placebo | Drug | Intravenous infusion in regular intervals over 6 months |
|
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Concentration of anti-felzartamab antibodies in serum (ELISA, ng/mL)
| At day 0, week 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 44, 48 and 52 |
| Morphologic ABMR categories | Phenotyping of renal transplant biopsies: active ABMR vs. chronic active ABMR vs. chronic inactive ABMR | At week 24 and at week 52 |
| Serum donor-specific antibody (DSA) levels | Mean fluorescence intensity (MFI) of the immunodominant DSA (Luminex) | Week 0, 12, 24, and 52 |
| Serum immunoglobulin levels | Ig (sub)classes (ELISA, Nephelometry, mg/dL) | Week 0, 12, 24, and 52 |
| Leukocyte subsets in peripheral blood | Counts of circulating plasma cells, natural killer cells, T and B cell subpopulations (flow cytometry, cell counts) | Week 0, 1, 4, 8, 12, 24, and 52 |
| Immunologic biomarkers | CXCL9 and CXCL10 levels in blood and urine, BAFF levels in blood (ELISA, Luminex) | Week 0, 12, 24, and 52 |
| Torque Teno virus | Torque Teno virus (TTV) levels in plasma (quantitative PCR) | Week 0, 12, 24, and 52 |
| eGFR | Estimated GFR (CKD-EPI, mL/min/1.73m2) | At day 0, week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 44, 48 and 52 |
| Proteinuria | Urinary protein excretion in spot urine (protein/creatinine ratio in mg/g) | At day 0, week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 44, 48 and 52 |
| Graft loss | Graft failure: time (months) to event (Kaplan Meier) | 12 months |
| Death | Patient death: time (months) to event (Kaplan Meier) | 12 months |
| Glomerulitis plus peritubular capillaritis sum score | Grading of renal transplant biopsies using a semiquantitative score (g+ptc 0-6); higher = worse prognosis | At week 24 and at week 52 |
| Transplant glomerulopathy score | Grading of renal transplant biopsies using a semiquantitative score (cg 0-3); higher = worse prognosis | At week 24 and at week 52 |
| C4d score | Grading of renal transplant biopsies using a semiquantitative score (c4d 0-3); higher = worse prognosis | At week 24 and at week 52 |
| Molecular ABMR score | ABMR score (0.0-1.0, dimensionless number) assessed via the Molecular Microscope Diagnostic Platform (MMDx); higher = worse prognosis | At week 24 and at week 52 |
| Molecular ABMR categories | Molecular archetype analysis of rejection phenotypes using the Molecular Microscope Diagnostic Platform (MMDx). Phenotypes: early-stage ABMR; fully developed ABMR; late-stage ABMR | At week 24 and at week 52 |
| Berlin |
| 10117 |
| Germany |
| Background |
| Raab MS, Engelhardt M, Blank A, Goldschmidt H, Agis H, Blau IW, Einsele H, Ferstl B, Schub N, Rollig C, Weisel K, Winderlich M, Griese J, Hartle S, Weirather J, Jarutat T, Peschel C, Chatterjee M. MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1-2a trial. Lancet Haematol. 2020 May;7(5):e381-e394. doi: 10.1016/S2352-3026(19)30249-2. Epub 2020 Mar 11. |
| 33315763 | Background | Mayer KA, Doberer K, Eskandary F, Halloran PF, Bohmig GA. New concepts in chronic antibody-mediated kidney allograft rejection: prevention and treatment. Curr Opin Organ Transplant. 2021 Feb 1;26(1):97-105. doi: 10.1097/MOT.0000000000000832. |
| 40444214 | Derived | Mayer KA, Budde K, Diebold M, Halloran PF, Bohmig GA. Targeting CD38 in Antibody-Mediated Rejection. Transpl Int. 2025 May 15;38:14343. doi: 10.3389/ti.2025.14343. eCollection 2025. |
| 39780312 | Derived | Madill-Thomsen KS, Gauthier PT, Abouljoud M, Bhati C, Bruno D, Ciszek M, Durlik M, Feng S, Foroncewicz B, Grat M, Jurczyk K, Levitsky J, McCaughan G, Maluf D, Montano-Loza A, Moonka D, Mucha K, Myslak M, Perkowska-Ptasinska A, Piecha G, Reichman T, Tronina O, Wawrzynowicz-Syczewska M, Zeair S, Halloran PF. Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study. Transplantation. 2025 Aug 1;109(8):1367-1382. doi: 10.1097/TP.0000000000005269. Epub 2025 Jan 9. |
| 38804514 | Derived | Mayer KA, Schrezenmeier E, Diebold M, Halloran PF, Schatzl M, Schranz S, Haindl S, Kasbohm S, Kainz A, Eskandary F, Doberer K, Patel UD, Dudani JS, Regele H, Kozakowski N, Klager J, Boxhammer R, Amann K, Puchhammer-Stockl E, Vietzen H, Beck J, Schutz E, Akifova A, Firbas C, Gilbert HN, Osmanodja B, Halleck F, Jilma B, Budde K, Bohmig GA. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. N Engl J Med. 2024 Jul 11;391(2):122-132. doi: 10.1056/NEJMoa2400763. Epub 2024 May 25. |
| 35395951 | Derived | Mayer KA, Budde K, Halloran PF, Doberer K, Rostaing L, Eskandary F, Christamentl A, Wahrmann M, Regele H, Schranz S, Ely S, Firbas C, Schorgenhofer C, Kainz A, Loupy A, Hartle S, Boxhammer R, Jilma B, Bohmig GA. Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial. Trials. 2022 Apr 8;23(1):270. doi: 10.1186/s13063-022-06198-9. |